Douglas C. Bauer, MD is an Associate Professor of Medicine, and Epidemiology and Biostatistics at the University of California, San Francisco, with an established track record as a researcher, educator, and clinician. After completing fellowship training in clinical epidemiology in 1992, Dr Bauer undertook a 3 year mentored career development award with Dr. Steven Cummings. He is currently Director of Research for the Division of General Internal Medicine, and is a core faculty member of the UCSF Coordinating Center (UCSF CC). The candidate proposes building a program of patient-oriented research focused on the use of biomarkers in musculoskeletal and aging research. The objectives of the program are to promote patient-oriented research at UCSF among medical residents, fellows, and junior faculty, and to provide junior investigators with opportunities to better understand biomarker methodology and utilize biomarkers in their research. Using the many clinical research training resources available at UCSF and several large osteoporosis clinical trial databases available to Dr. Bauer through the UCSF CC, the overall aims of this program are: 1) to mentor medical residents, clinical research fellows, and junior faculty to conduct patient-oriented research;2) to provide expertise and opportunities for mentees who wish to utilize biomarkers in patient-oriented musculoskeletal research and 3) to advance our understanding of biomarkers in osteoporosis. The specific aims of Dr. Bauer's research plan are: 1) To determine differences in the anti-fracture efficacy of several anti-resorptive treatments for osteoporosis defined by baseline levels of selected biomarkers, including estradiol and markers of bone turnover;2) To compare the adequacy of change in biochemical markers of bone turnover to serve as a surrogate for fracture outcomes in clinical trials of alendronate, raloxifene, and estrogen-progestin;and 3) To compare the degree of mediation of the anti-fracture effect of several osteoporosis treatments, including alendronate, raloxifene, and estrogen-progestins, by change in BMD as well as change in biochemical markers of bone turnover. Funding of this K24 will allow Dr. Bauer to reduce his clinical and administrative responsibilities, and focus his efforts on promoting and teaching patient-oriented research.